The rabbit MHC locus, designated RLA, encodes class I and class II molecules similar to those encoded in the human and murine systems. The rabbit class I family contains only between 8 to 13 genes, so is smaller than its human or murine counterparts. In contrast with the other systems, a single class I protein has been found in association with the beta-2 microglobulin at the surface of cells from a rabbit T cell line RL-5. Structural data are now available for four cDNA clones, and the genes corresponding to three of these have been partially or completely sequenced. The gene 19-1 has been shown to encode the expressed class I proteins. Expression studies have been done in normal rabbit tissues using probes derived from these clones. One of the cDNA clones, designated pR27, is transcribed only in the T cell line and in rabbit thymus, and at lower levels in lymphoid tissues containing T cells. Even though pR27 has, like the murine Tla gene product, an unusual splicing pattern, no structural homology to the Tla was seen and the specificity of their expression might be different. Therefore, pR27 most likely represents a novel T cell specific class I gene. Two other genes, 19-1 and 5-2, were shown to be transcribed in all the tissues and cell lines studied. This differential pattern of expression observed among the rabbit class I genes will provide a system to study mechanisms involved in regulation of expression of these genes. Search for sequences and factors involved in normal and tissue-specific expression are now in progress. Studies of the class II genes revealed that there are rabbit genes corresponding to every gene observed in the HLA-D region. Class II alpha genes corresponding to HLA-Dr, -DP, -DQ, and -DZ, as well as the counterpart of the HLA-DO beta gene, have now been observed. A gene remnant has also been found in the rabbit genome, and consists of sequences corresponding to a class II alpha gene intron 4, followed by exon 4, flanked by direct repeats. Studies on the class II genes are now concentrating on the tissue-specific expression of these different genes.